Ketones enohzation

The methyl ketone shown in the example can enohze in only one direction and typifies the kind of reactant that can be converted to a carboxylic acid in synthetically accept able yield by the haloform reaction When C 3 of a methyl ketone bears enolizable hydro O... 

A similar approach was carried out reacting an enohzable ketone with amides in the presence of the hypervalent iodine(III) reagent (hydroxy(tosyl-oxy)iodobenzene, HDNIB) [48]. The reaction was carried out imder solvent-... 

N,N-Bis(trimethylsilyl)carbodiimide 328, which is readily accessible in 81% yield on silylation of cyanamide with TCS 14/triethylamine [124] and which is apparently in equilibrium with N,N-bis(trimefhylsilyl)cyanamide 553, reacts readily with non-enolizable ketones such as 554 or 2,5-dimethyl-p-quinone in the presence of CsF or TiCL., probably via 553, to N-cyanoimines such as 555 or 556, in 47 and 89% yield, respectively, and HMDSO 7 [125, 126] whereas the enohzable ketone... 

An investigation of keto-enol tautomerism for perfluorinated keto-enol systems was undertaken. N-methylpyrrolidone (NMP) catalyzes equilibration of the keto and enol forms, but if used in more than trace amounts, it drives the equilibrium strongly toward enol because of hydrogen bonding to the amide. The enol is much more thermodynamically stable than its ketone, and it was found that in mildly Lewis basic solvents, such as ether, THE, acetonitrile, and NMP, the enohzation equilibrium lies too far right to allow detection of ketone (Correa et al., 1994). 

Interestingly, mixed magnesate reagents, RMe2MgLi (R Me), conld transfer the R group selectively to ketones (equations 15-18). Snrprisingly, readily enohzable ketones such as /3-tetralone were ethylated in excellent yields (eqnation 18). 

In this case, alkene insertion into the h-H bond is likely to occur first, producing a linear alkyl species. CO insertion would produce an acyl species, which would then be followed by reductive elimination of the acylsilane product. Enohzation, followed by rapid reaction of HSiR3 with the OH group, traps out the enol silyl ether. The Hy produced Irom this sUylation step is used to hydrogenate some of the starting alkene. Thus, the maximum yield will generally be only 66% of the enol silyl ether product. The enol silyl ethers can be readily converted into silyl ketones (equation 10). 

The aza-enolate reacts cleanly with other aldehydes or ketones to give aldol products. Even the most challenging of cross-couplings—attack on another similar enoHzable aldehyde—occurs in... 

In addition, high h-enohzation stereoselectivity is observed for benzylic ketones (Scheme 3.37) [26],... 

Although many of these reactions proceed in nearly quantitative yield, a few result in poor yields. Poor yields are most likely to be encountered in the synthesis of tertiary alcohols with bulky alkyl groups in which side reactions compete more effectively. The two most important side reactions are enohzation and reduction. Enolization can occur if the ketone has at least one hydrogen atom on either of the a-carbons and reduction can occur when the R of the Grignard reagent has hydrogen on its -carbon. 

The original Mannich reaction is the acid-catalyzed aminomethylation of enohz-able ketones with non-enolizable aldehydes and ammonia, primary amines, or secondary amines, which involves nucleophilic addition of ketone enols to iminium salts generated in situ from the aldehydes and the nitrogen compounds [183]. This three-component coupling reaction provides a powerful tool for carbon-carbon bond formation and introduction of nitrogen functionality. The classical Mannich reaction has some drawbacks in reaction efficiency, regioselectivity, and appli-... 

In turn, a,p-unsaturated aldehydes or ketones (326, 329) can be enoHzed by Huenig s base before being trapped by support-bound silyl chlorides. The resulting support link is very labile and a ketone is released from the support upon treatment with TFA [312]. Some examples of these Diels-Alder reactions can be seen in Scheme 69. 

Organolanthanum reagents For nucleophihc addition to easily enohzed ketones harder nucleophiles are preferred. Arylithiums, derived from iV-Boc arylamines by o,iV-dilithiation with t-BuLi, are treated with LaCls 2LiCl in THF before reaction with iV-Boc 3-pyrrohdinone to give precursors of Ab-Boc hyptamines. ... 

If you want a more controlled reaction with addition of formaldehyde to an aldehyde or ketone without the reduction step, you can sometimes succeed with a weaker base such as potassium carbonate. Typically in these reactions all the enoHzable hydrogen atoms (green) are replaced by molecules of formaldehyde (black). 

Claisen condensations always involve esters as the electrophilic partner, but enolates of other carbonyl compounds—ketones, for example—may work equally well as the enoi partner. In a reaction with a carbonate, only the ketone can enolize and the reactive carbonate ester is more electrophilic than another molecule of the ketone. A good example is this reaction of cyclooctanone. It does not matter which side of the carbonyl group enoHzes—they are both the same. 

Diketones. Saegusa et al. have reported the synthesis of 1,4-diketones by treatment of Uthium enolates of methyl ketones with cupric chloride (1 eq.) in DMF at -78°. Yields of coupled products are high in the case of ketones with only one enohzable hydrogen (pinacolone and acetophenone) ... 

Alkyl chlorides. Hungarian chemists have isolated and identified the salts (1) and (2) in the reaction of triphenylphosphine and carbon tetrachloride with alcohols, enohzable ketones, and acid halides. They have suggested a new mechanism in which these salts participate. 

The first problem has two possible solutions by direct acylation, labelled A and B in the diagram. A would have to be controlled as the straight chain ester could self-condense. B needs no control as only the ketone can enohze. Diethyl carbonate (EtO)2CO is more electrophilic than a ketone and only the wanted product can enolize again and form a stable enolate under the reaction conditions. However, route B adds only one carbon atom. 

A common entry into the DKR manifold involves racemization of stereocenters a to carbonyl groups. The achiral intermediate formed through base-catalyzed enoHzation allows for facile racemization of the substrate. a-Substituted p-dicarbonyl compounds racemize under particularly mild conditions and undergo highly enantioselective dynamic kinetic resolutions by hydrogenation of the ketone unit to form a-substituted (3-hydroxy carbonyl compounds (Figure 14.30). This type of DKR is used to prepare azetidinone, which is a key intermediate in the synthesis of carbapenem antibiotics on an industrial scale (i.e., 120 ton/year). ... 

Paterson et al. reported several examples of enoHzations of propionate esters in the presence of ketones bearing two different enolizable hydrogens using an internal quench protocol (Scheme 4.46) [49]. The conformation of the highly congested ketone presumably inhibited abstraction of the a-keto protons. However, concentrations of LDA greater than 15 mM resulted in 10-20% of elimination products resulting from ketone enolization. 

Enohzable carbonyl compounds could also be employed in the gold(III)-catalyzed [4+2] cycloaddition with 2-alkynylbenzaldehydes to give the corresponding naphthyl ketones (Scheme 21.43) [50]. This reaction may proceed via the inverse electron demand Diels-Alder reaction of benzopyrylium intermediates with the enol form of carbonyl compounds followed by dehydration. 

Rates of enolization can be measured in several ways. One method involves determining the rate of halogenation of the ketone. In the presence of a sufficient concentration of bromine or iodine, halogenation is much faster than enohzation or its reverse and can therefore serve to measure the rate of enolization ... 

The potential of 9 as a chiral Lewis base catalyst was further demonstrated by application to the aldol reaction of trichlorosilyl enol ethers of ketones with aldehydes, which proceeded with high diastereo- and enantioselectivity [32], The observed stereospecificity suggested the intervention of a six-membered cyclic transition state (Scheme 7.17). Notably, enoHzation of cyclohexanone derivatives and aliphatic aldehydes appeared feasible by SiCLt with the assistance of amine base and 9, leading to the estabhshment of a new protocol for direct aldol-type reactions between ketones and aldehydes or two aldehydes (Scheme 7.18) [33]. 

Tada, K. and Miura, K., The photo-enoHzation of P-disubstituted a,P-unsaturated ketones. Bull. Soc. Chim. Jpn., 49, 713,1976. 

A. C., Direct measurement of the rates of reketonization of dienolates produced by photochemical enohzation of 3-alkyl a,P-unsaturated ketones in aqueous basic solution, /. Am. Chem. Soc., 109, 2479, 1987. 

One can prevent the above processes from occurring by preparing the ketone radical cations in solid media at low temperature, to prevent their diffusion and their reaching suitable conformations for spontaneous fragmentation. In the early 1990s, our laboratory and that of J. G bicki at the Lodz University of Technology (Poland) initiated a joint program to explore the scope of enohzations induced by ionization (or electron-transfer), the electronic structure of the involved radical... 

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